Neonatology pp 469-483 | Cite as

Bronchopulmonary Dysplasia/Chronic Lung Disease

  • Vineet Bhandari


Bronchopulmonary dysplasia (BPD) is the most common cause of chronic lung disease in infancy [1]. The consensus definition of BPD has been summarized in Table 65.1. The “classic” BPD described by Northway in 1967 has now been replaced by less severe forms of “new” BPD, which are infrequently found in patients >30 weeks of gestation and with birth weights (BW) >1200 grams. Presently, infants who weigh <1250 grams account for 97% of all BPD patients [2]. The incidence of BPD, defined as oxygen need at 36 weeks post-menstrual age (PMA), was 52% (BW 501–750 g), 34% (BW 751–1000 g), 15% (BW 1001–1200g), and 7% (BW 1201–1500 g). Using a physiologic definition based on an oxygen reduction challenge at 36 weeks PMA led to a 10% decrease in the incidence of BPD.


Vascular Endothelial Growth Factor Hepatocyte Growth Factor Migration Inhibitory Factor Keratinocyte Growth Factor Nasal Continuous Positive Airway Pressure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Baraldi E, Filippone M (2007) Chronic lung disease after premature birth. N Engl J Med 357: 1946–1955PubMedCrossRefGoogle Scholar
  2. 2.
    Walsh MC, Szefler S, Davis J et al (2006) Summary proceedings from the bronchopulmonary dysplasia group. Pediatrics 117: S52–S56PubMedGoogle Scholar
  3. 3.
    Coalson JJ (2006) Pathology of bronchopulmonary dysplasia. Semin Perinatol 30: 179–184PubMedCrossRefGoogle Scholar
  4. 4.
    Bhandari V, Bizzarro MJ, Shetty A et al (2006) Familial and genetic susceptibility to major neonatal morbidities in preterm twins. Pediatrics 117: 1901–1906PubMedCrossRefGoogle Scholar
  5. 5.
    Lavoie PM, Pham C, Jang KL (2008) Heritability of bronchopulmonary dysplasia, defined according to the consensus statement of the national institutes of health. Pediatrics 122: 479–485PubMedCrossRefGoogle Scholar
  6. 6.
    Bokodi G, Treszl A, Kovacs L et al (2007) Dysplasia: a review. Pediatr Pulmonol 42: 952–961PubMedCrossRefGoogle Scholar
  7. 7.
    Bhandari V, Gruen JR (2006) The genetics of bronchopulmonary dysplasia. Semin Perinatol 30: 185–191PubMedCrossRefGoogle Scholar
  8. 8.
    Van Marter LJ, Dammann O, Allred EN et al (2002) Chorioamnionitis, mechanical ventilation, and postnatal sepsis as modulators of chronic lung disease in preterm infants. J Pediatr 140: 171–176PubMedCrossRefGoogle Scholar
  9. 9.
    Bhandari V, Elias JA (2006) Cytokines in tolerance to hyperoxiainduced injury in the developing and adult lung. Free Radic Biol Med 41: 4–18PubMedCrossRefGoogle Scholar
  10. 10.
    Bhandari A, Bhandari V (2003) Pathogenesis, pathology and pathophysiology of pulmonary sequelae of bronchopulmonary dysplasia in premature infants. Front Biosci 8: e370–e380PubMedCrossRefGoogle Scholar
  11. 11.
    Bhandari A, Bhandari V (2007) Bronchopulmonary dysplasia: an update. Indian J Pediatr 74: 73–77PubMedCrossRefGoogle Scholar
  12. 12.
    Speer CP (2006) Inflammation and bronchopulmonary dysplasia: a continuing story. Semin Fetal Neonatal Med 11: 354–362PubMedCrossRefGoogle Scholar
  13. 13.
    Ryan RM, Ahmed Q, Lakshminrusimha S (2008) Inflammatory mediators in the immunobiology of bronchopulmonary dysplasia. Clin Rev Allergy Immunol 34: 174–190PubMedCrossRefGoogle Scholar
  14. 14.
    Thomson A, Bhandari V (2008) Pulmonary biomarkers of bronchopulmonary dysplasia. Biomark Insights 3: 361–373Google Scholar
  15. 15.
    Bhandari V, Choo-Wing R, Lee CG et al (2006) Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death. Nat Med 12: 1286–1293PubMedCrossRefGoogle Scholar
  16. 16.
    Aghai ZH, Faqiri S, Saslow JG et al (2007) Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: attenuation by dexamethasone. J Perinatol 28: 149–155PubMedCrossRefGoogle Scholar
  17. 17.
    Baier RJ, Majid A, Parupia H et al (2004) CC chemokine concentrations increase in respiratory distress syndrome and correlate with development of bronchopulmonary dysplasia. Pediatr Pulmonol 37: 137–148PubMedCrossRefGoogle Scholar
  18. 18.
    Kevill K, Bhandari V, Kettuman M et al (2008) A role for macrophage migration inhibitory factor in the neonatal respiratory distress syndrome. J Immunol 180: 601–608PubMedGoogle Scholar
  19. 19.
    Cederqvist K, Sorsa T, Tervahartiala T et al (2001) Matrix metalloproteinases-2, -8, and -9 and TIMP-2 in tracheal aspirates from preterm infants with respiratory distress. Pediatrics 108: 686–692PubMedCrossRefGoogle Scholar
  20. 20.
    Rehan V, Torday J (2006) Lower parathyroid hormone related protein content of tracheal aspirates in very low birth weight infants who develop bronchopulmonary dysplasia. Pediatr Res 60: 216–220PubMedCrossRefGoogle Scholar
  21. 21.
    Niu JO, Munshi U, Siddiq M et al (1998) Early increase in endothelin-1 in tracheal aspirates of preterm infants:correlation with bronchopulmonary dysplasia. J Pediatr 132: 965–970PubMedCrossRefGoogle Scholar
  22. 22.
    Ambalavanan N, Novak ZE (2003) Peptide growth factors in tracheal aspirates of mechanically ventilated preterm neonates. Pediatr Res 53: 240–244PubMedCrossRefGoogle Scholar
  23. 23.
    Thebaud B, Abman S (2007) Bronchopulmonary dysplasia- where have all the vessels gone? Role of angiogenic growth factors inchronic lung disease. Am J Respir Crit Care Med 175: 978–985PubMedCrossRefGoogle Scholar
  24. 24.
    Bhandari V, Choo-Wing R, Lee CG et al (2008) Developmental regulation of NO-mediated VEGF-induced effects in the lung. Am J Respir Cell Mol Biol 39: 420–430PubMedCrossRefGoogle Scholar
  25. 25.
    Ekekezie, II, Thibeault DW, Simon SD et al (2004) Low levels of tissue inhibitors of metalloproteinases with a high matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio are present in tracheal aspirate fluids of infants who develop chronic lung disease. Pediatrics 113: 1709–1714PubMedCrossRefGoogle Scholar
  26. 26.
    Vento G, Capoluongo E, Matassa PG et al (2006) Serum levels of seven cytokines in premature, ventilated newborns, correlation with old and new forms of bronchopulmonary dysplasia. Intensive Care Med 32: 723–730PubMedCrossRefGoogle Scholar
  27. 27.
    Cullen A, Van Marter LJ, Allred EN et al (2002) Urine bombesinlike peptide elevation precedes clinical evidence of bronchopulmonary dysplasia. Am J Respir Crit Care Med 165: 1093–1097PubMedGoogle Scholar
  28. 28.
    Bland RD, Xu L, Ertsey R et al (2007) Dysregulation of pulmonary elastin synthesis and assembly in preterm lambs with chronic lung disease. Am J Physiol Lung Cell Mol Physiol 292: L1370–1384PubMedCrossRefGoogle Scholar
  29. 29.
    Hirakawa H, Pierce RA, Bingol-Karakoc G et al (2007) Cathepsin S deficiency confers protection from neonatal hyperoxia-induced lung injury. Am J Respir Crit Care Med 176: 778–785PubMedCrossRefGoogle Scholar
  30. 30.
    Padela S, Cabacungan J, Shek S et al (2005) Hepatocyte growth factor is required for alveologenesis in the neonatal rat. Am J Respir Crit Care Med 172: 907–914PubMedCrossRefGoogle Scholar
  31. 31.
    Frank L (2003) Protective effect of keratinocyte growth factor against lung abnormalities associated with hyperoxia in prematurely born rats. Biol Neonate 83: 263–272PubMedCrossRefGoogle Scholar
  32. 32.
    Bry K, Whitsett JA, Lappalainen U (2007) IL-1beta disrupts postnatal lung morphogenesis in the mouse. Am J Respir Cell Mol Biol 36: 32–42PubMedCrossRefGoogle Scholar
  33. 33.
    Choo-Wing R, Nedrelow JH, Homer RJ et al (2007) Developmental differences in the responses of IL-6 and IL-13 transgenic mice exposed to hyperoxia. Am J Physiol Lung Cell Mol Physiol 293: L142–L150PubMedCrossRefGoogle Scholar
  34. 34.
    Vozzelli MA, Mason SN, Whorton MH et al (2004) Antimacrophage chemokine treatment prevents neutrophil and macrophage influx in hyperoxia-exposed newborn rat lung. Am J Physiol Lung Cell Mol Physiol 286: L488–L493PubMedCrossRefGoogle Scholar
  35. 35.
    Vicencio AG, Lee CG, Cho SJ et al (2004) Conditional overexpression of bioactive transforming growth factor-beta1 in neonatal mouse lung: a new model for bronchopulmonary dysplasia? Am J Respir Cell Mol Biol 31: 650–656PubMedCrossRefGoogle Scholar
  36. 36.
    Thebaud B, Ladha F, Michelakis ED et al (2005) Vascular endothelial growth factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in alveolarization. Circulation 112: 2477–2486PubMedCrossRefGoogle Scholar
  37. 37.
    Subramaniam M, Bausch C, Twomey A et al (2007) Bombesin-like peptides modulate alveolarization and angiogenesis in bronchopulmonary dysplasia. Am J Respir Crit Care Med 176: 902–912PubMedCrossRefGoogle Scholar
  38. 38.
    Agrons A, Courtney S, Stocker J et al (2005) From the archives of the AFIP: Lung disease in premature neonates: radiologic-pathologic correlation. Radiographics 25: 1047–1073PubMedCrossRefGoogle Scholar
  39. 39.
    Bhandari A, Panitch HB (2006) Pulmonary outcomes in bronchopulmonary dysplasia. Semin Perinatol 30: 219–226PubMedCrossRefGoogle Scholar
  40. 40.
    Doyle LW, Faber B, Callanan C et al (2006) Bronchopulmonary dysplasia in very low birth weight subjects and lung function in late adolescence. Pediatrics 118: 108–113PubMedCrossRefGoogle Scholar
  41. 41.
    Hofhuis W, Huysman MW, van der Wiel EC et al (2002) Worsening of V′maxFRC in infants with chronic lung disease in the first year of life: a more favorable outcome after high-frequency oscillation ventilation. Am J Respir Crit Care Med 166: 1539–1543PubMedCrossRefGoogle Scholar
  42. 42.
    Short EJ, Kirchner HL, Asaad GR et al (2007) Developmental sequelae in preterm infants having a diagnosis of bronchopulmonary dysplasia: analysis using a severity-based classification system. Arch Pediatr Adolesc Med 161: 1082–1087PubMedCrossRefGoogle Scholar
  43. 43.
    Anderson PJ, Doyle LW (2006) Neurodevelopmental outcome of bronchopulmonary dysplasia. Semin Perinatol 30: 227–232PubMedCrossRefGoogle Scholar
  44. 44.
    Ehrenkranz RA, Walsh MC, Vohr BR et al (2005) Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics 116: 1353–1360PubMedCrossRefGoogle Scholar
  45. 45.
    Jeng SF, Hsu CH, Tsao PN et al (2008) Bronchopulmonary dysplasia predicts adverse developmental and clinical outcomes in verylow-birthweight infants. Dev Med Child Neurol 50: 51–57PubMedCrossRefGoogle Scholar
  46. 46.
    Watterberg KL, Gerdes JS, Cole CH et al (2004) Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Pediatrics 114: 1649–1657PubMedCrossRefGoogle Scholar
  47. 47.
    Howlett A, Ohlsson A (2003) Inositol for respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev:CD000366Google Scholar
  48. 48.
    Stevens TP, Harrington EW, Blennow M et al (2007) Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev 3:CD003063Google Scholar
  49. 49.
    Morley CJ, Davis PG, Doyle LW et al (2008) Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 358: 700–708PubMedCrossRefGoogle Scholar
  50. 50.
    Bhandari V, Gavino RG, Nedrelow JH et al (2007) A randomized controlled trial of synchronized nasal intermittent positive pressure ventilation in RDS. J Perinatol 27: 697–703PubMedCrossRefGoogle Scholar
  51. 51.
    Kugelman A, Feferkorn I, Riskin A et al (2007) Nasal intermittent mandatory ventilation versus nasal continuous positive airway pressure for respiratory distress syndrome: a randomized, controlled, prospective study. J Pediatr 150: 521–526PubMedCrossRefGoogle Scholar
  52. 52.
    Barrington KJ, Finer NN (2007) Inhaled nitric oxide for preterm infants: a systematic review. Pediatrics 120: 1088–1099PubMedCrossRefGoogle Scholar
  53. 53.
    Davis JM, Parad RB, Michele T et al (2003) Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase. Pediatrics 111: 469–476PubMedCrossRefGoogle Scholar
  54. 54.
    Pfister RH, Soll RF, Wiswell T (2007) Protein containing synthetic surfactant versus animal derived surfactant extract for the prevention and treatment of respiratory distress syndrome. Cochrane Database Syst Rev 4:CD006069Google Scholar
  55. 55.
    Bell EF, Acarregui MJ (2008) Restricted versus liberal water intake for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev 1:CD000503Google Scholar
  56. 56.
    Bhandari A, Bhandari V (2009) Pitfalls, problems and progress in bronchopulmonary dysplasia. Pediatrics 123: 1562–1573PubMedCrossRefGoogle Scholar
  57. 57.
    Greenough A (2007) How has research in the past 5 years changed my clinical practice. Arch Dis Child Fetal Neonatal Ed 92: F404–F407PubMedCrossRefGoogle Scholar
  58. 58.
    Yost CC, Soll RF (2000) Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2:CD001456Google Scholar
  59. 59.
    Kamlin CO, Davis PG (2004) Long versus short inspiratory times in neonates receiving mechanical ventilation. Cochrane Database Syst Rev 4:CD004503Google Scholar
  60. 60.
    Ambalavanan N, Carlo WA (2006) Ventilatory strategies in the prevention and management of bronchopulmonary dysplasia. Semin Perinatol 30: 192–199PubMedCrossRefGoogle Scholar
  61. 61.
    Bhandari V (2006) Non-invasive ventilation of the sick neonate: evidence-based recommendations. J Neonat 20: 214–221Google Scholar
  62. 62.
    Miller JD, Carlo WA (2007) Safety and effectiveness of permissive hypercapnia in the preterm infant. Curr Opin Pediatr 19: 142–144PubMedCrossRefGoogle Scholar
  63. 63.
    Henderson-Smart DJ, Davis PG (2003) Prophylactic methylxanthines for extubation in preterm infants. Cochrane Database Syst Rev 1:CD000139Google Scholar
  64. 64.
    Schmidt B, Roberts RS, Davis P et al (2006) Caffeine therapy for apnea of prematurity. N Engl J Med 354: 2112–2121PubMedCrossRefGoogle Scholar
  65. 65.
    Tyson JE, Wright LL, Oh W et al (1999) Vitamin A supplementation for extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med 340: 1962–1968PubMedCrossRefGoogle Scholar
  66. 66.
    Darlow BA, Graham PJ (2007) Vitamin A supplementation to prevent mortality and short and long-term morbidity in very low birthweight infants. Cochrane Database Syst Rev 4:CD000501Google Scholar
  67. 67.
    Bhandari V, Brodsky N, Porat R (2005) Improved outcome of extremely low birth weight infants with Tegaderm application to skin. J Perinatol 25: 276–281PubMedCrossRefGoogle Scholar
  68. 68.
    Oh W, Poindexter BB, Perritt R et al (2005) Association between Fluid Intake and Weight Loss during the First Ten Days of Life and Risk of Bronchopulmonary Dysplasia in Extremely Low Birth Weight Infants. J Pediatr 147: 786–790PubMedCrossRefGoogle Scholar
  69. 69.
    Lai NM, Rajadurai SV, Tan KH (2006) Increased energy intake for preterm infants with (or developing) bronchopulmonary dysplasia/chronic lung disease. Cochrane Database Syst Rev 3:CD005093Google Scholar
  70. 70.
    Halliday HL, Ehrenkranz RA, Doyle LW (2003) Delayed (JO THERESA3weeks) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev 1:CD001145Google Scholar
  71. 71.
    Halliday HL, Ehrenkranz RA, Doyle LW (2003) Moderately early (7–14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev 1:CD001144Google Scholar
  72. 72.
    Halliday HL, Ehrenkranz RA, Doyle LW (2003) Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev 1:CD001146Google Scholar
  73. 73.
    Baveja R, Christou H (2006) Pharmacological strategies in the prevention and management of bronchopulmonary dysplasia. Semin Perinatol 30: 209–218PubMedCrossRefGoogle Scholar
  74. 74.
    Khemani E, McElhinney DB, Rhein L et al (2007) Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era. Pediatrics 120: 1260–1269PubMedCrossRefGoogle Scholar
  75. 75.
    Bhandari A, Schramm CM, Kimble C et al (2008) Effect of a short course of prednisolone in infants with oxygen-dependent bronchopulmonary dysplasia. Pediatrics 121: e344–e349PubMedCrossRefGoogle Scholar
  76. 76.
    Ng GY, da S, Ohlsson A (2001) Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants. Cochrane Database Syst Rev 3:CD003214Google Scholar
  77. 77.
    Brundage KL, Mohsini KG, Froese AB et al (1990) Bronchodilator response to ipratropium bromide in infants with bronchopulmonary dysplasia. Am Rev Respir Dis 142: 1137–1142PubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Vineet Bhandari
    • 1
  1. 1.Department of Pediatrics, Obstetrics, Gynecology and Reproductive SciencesYale University School of MedicineNew HavenUSA

Personalised recommendations